The Involvement of CD44 and Its Novel Ligand Galectin-8 in Apoptotic Regulation of Autoimmune Inflammation

• Published in: Journal of Immunology 2007-07, Vol.179 (2), p.1225-1235
• Main Authors: Eshkar Sebban, Lora, Ronen, Denise, Levartovsky, David, Elkayam, Ori, Caspi, Dan, Aamar, Suhail, Amital, Howard, Rubinow, Alan, Golan, Ira, Naor, David, Zick, Yehiel, Golan, Itshak
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - metabolism; Autoimmune Diseases - metabolism; Blotting, Western; Chromatography, Affinity; Cloning, Molecular; Fibrinogen - metabolism; Flow Cytometry; Galectins - metabolism; Humans; Hyaluronan Receptors - metabolism; Immunoprecipitation; Inflammation - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - immunology; Surface Plasmon Resonance; Synovial Fluid - chemistry; Transfection
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.2.1225

The synovial fluid (SF) cells of rheumatoid arthritis (RA) patients express a specific CD44 variant designated CD44vRA. Using a cellular model of this autoimmune disease, we show in this study that the mammalian lectin, galectin-8 (gal-8), is a novel high-affinity ligand of CD44vRA. By affinity chromatography, flow cytometry, and surface plasmon resonance, we demonstrate that gal-8 interacts with a high affinity (K(d), 6 x 10(-9) M) with CD44vRA. We further demonstrate that SF cells from RA patients express and secrete gal-8, to a concentration of 25-65 nM, well within the concentration of gal-8 required to induce apoptosis of SF cells. We further show that not all gal-8 remains freely soluble in the SF and at least part forms triple complexes with CD44 and fibrinogen that can be detected, after fibrinogen immunoprecipitation, with Abs against fibrinogen, gal-8 and CD44. These triple complexes may therefore increase the inflammatory reaction by sequestering the soluble gal-8, thereby reducing its ability to induce apoptosis in the inflammatory cells. Our findings not only shed light on the receptor-ligand relationships between CD44 and gal-8, but also underline the biological significance of these interactions, which may affect the extent of the autoimmune inflammatory response in the SF of RA patients.